Skeletal muscle function is essential for health, and it depends on the proper activity of myofibers and their innervating motor neurons. Each adult muscle is composed of different types of myofibers with distinct contractile and metabolic characteristics. The proper balance of myofiber types is disrupted in most muscle degenerative disorders, representing another factor compromising muscle function. One promising therapeutic approach for the treatment of these diseases is cell replacement based on the targeted differentiation of pluripotent stem cells (PSCs) towards the myogenic lineage. We have previously shown that transient induction of Pax3 or Pax7 in PSCs allows for the generation of skeletal myogenic progenitors endowed with myogenic regenerative potential, but whether they contribute to different fiber types remains unknown. Here, we investigate the fiber type composition of mouse PSC-derived myofibers upon their transplantation into dystrophic and non-dystrophic mice. Our data reveal that PSC-derived myofibers express slow and oxidative myosin heavy-chain isoforms, along with developmental myosins, regardless of the recipient background. Furthermore, transplantation of the mononuclear cell fraction re-isolated from primary grafts into secondary recipients results in myofibers that maintain preferential expression of slow and oxidative myosin heavy-chain isoforms but no longer express developmental myosins, thus indicating postnatal composition. Considering oxidative fibers are commonly spared in the context of dystrophic pathogenesis, this feature of PSC-derived myofibers could be advantageous for therapeutic applications.

中文翻译：

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多能干细胞衍生的骨骼肌纤维优先表达与慢速和氧化性肌肉相关的肌球蛋白重链同工型。

骨骼肌功能对于健康至关重要，它取决于肌纤维及其支配的运动神经元的正常活动。每个成年肌肉由具有不同收缩和代谢特征的不同类型的肌纤维组成。在大多数肌肉退行性疾病中，肌纤维类型的适当平衡受到破坏，这是损害肌肉功能的另一个因素。一种治疗这些疾病的有前途的治疗方法是基于多能干细胞（PSC）向成肌谱系的定向分化的细胞替代。先前我们已经表明，在PSC中瞬时诱导Pax3或Pax7可以产生具有肌再生潜力的骨骼肌成纤维祖细胞，但是尚不清楚它们是否有助于不同的纤维类型。这里，我们研究了小鼠PSC衍生的肌纤维移植入营养不良和非营养不良小鼠的纤维类型组成。我们的数据表明，无论受者背景如何，PSC衍生的肌纤维均表达缓慢的和氧化的肌球蛋白重链同工型，以及发育性肌球蛋白。此外，将从原代移植物重新分离的单核细胞级分移植到次要受体中会导致肌纤维保持慢速和氧化性肌球蛋白重链同工型的优先表达，但不再表达发育性肌球蛋白，因此表明产后组成。考虑到在营养不良的发病机制中通常不使用氧化纤维，因此源自PSC的肌纤维的这一特征对于治疗应用可能是有利的。